Summary & Overview
CPT 81237: EZH2 Variant Analysis (codon 646)
CPT code 81237 represents a targeted molecular diagnostic assay for detection of sequence variants in the EZH2 gene, including frequently observed alterations at codon 646. This code captures a specialized laboratory procedure used in oncology and hematopathology to identify somatic or germline EZH2 alterations that can inform diagnosis, prognosis, and therapeutic selection. The code matters nationally as precision oncology testing becomes more integrated into care pathways and payer coverage policies evolve to address molecularly guided treatment decisions. Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the clinical context for EZH2 testing, expected sites of service, common billing modifiers, and what typical coverage and reimbursement considerations look like across major national payers. The brief also provides benchmark-oriented insights on coding practice, documentation needs, and potential policy updates affecting molecular diagnostic claims. Data not available in the input for payor-specific rates, associated taxonomies, and ICD-10 pairings are noted where applicable.
Billing Code Overview
CPT code 81237 describes a molecular pathology test that detects specific variants in the enhancer of zeste 2 polycomb repressive complex 2 subunit gene (EZH2), with common targets such as changes in codon 646. The service is a targeted genetic variant test performed by a clinical laboratory analyst using molecular techniques to identify oncogenic or clinically relevant sequence alterations.
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Service type: Targeted molecular diagnostic test for single-gene variant detection
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Typical site of service: Clinical molecular pathology laboratory or hospital-based laboratory with molecular diagnostics capability
Clinical & Coding Specifications
Clinical Context
A 62-year-old patient with a history of diffuse large B-cell lymphoma presents with persistent or relapsed disease after frontline chemoimmunotherapy. The treating hematologist/oncologist orders molecular testing of a formalin-fixed paraffin-embedded (FFPE) tumor specimen to detect hotspot somatic variants in the enhancer of zeste 2 polycomb repressive complex 2 subunit gene (EZH2), commonly at codon 646. The clinical laboratory receives the specimen, performs DNA extraction, and runs a targeted molecular assay (e.g., PCR-based, Sanger sequencing, or next-generation sequencing panel focused on EZH2 hotspots). The technical lab analyst conducts the analytic process, generates variant calls, performs quality control, and produces a technical report of detected pathogenic or likely pathogenic variants for the pathologist or molecular director to interpret. Results are routed to the ordering clinician to inform prognosis and targeted therapy considerations, clinical trial eligibility, or further diagnostic workup.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
26 | Professional component | Use when billing only the professional (interpretive) component separate from the technical component for laboratory test interpretation by a pathologist or molecular geneticist. |
TC |